PROJECT IV: PRENATAL SCREENING AND MECHANISMS RESPONSIBLE FOR CRITICAL CONGENITAL HEART DISEASE IN MISSISSIPPI, A RURAL AND MEDICALLY UNDERSERVED POPULATION SUMMARY Congenital heart defects (CHDs) are the leading cause of infant deaths due to birth defects, occurring in nearly 40,000 newborns in the U.S. each year (~1% of all live births), and are one of the most common reasons for the use of health services among children with chronic conditions. Twenty five percent of CHDs are critical CHDs (CCHD), defined as those requiring surgical or catheter intervention in the first year of life for survival. In Mississippi (MS), the incidence of some CCHDs is higher than in other similar U.S. populations. The origins of most CHDs are thought to be multifactorial, involving genetic and environmental factors yet to be identified. Thus the reasons for the increased incidence of CCHDs in MS are unknown. Mississippi has one of the highest rates of obesity in the US, especially among African Americans. There have been few studies done evaluating the role of maternal obesity and the incidence of CCHD. Whether obesity and concomitant type II diabetes contribute to the increased incidence of CCHD in MS is not clear. Thus the studies proposed in this application will test the hypothesis that obesity and type II diabetes contribute to the increased incidence of CCHD in MS. Another potential reason for the increased incidence of CCHDs in MS may be undiagnosed consanguinity (blood relation between parents) among affected couples. According to 2012 US census data, approximately 72% of MS residents were born in MS. Limited migration among residents of MS compared to other states suggests that some level of unknown consanguinity might be prevalent. Thus the studies in this application will test the hypothesis that undiagnosed consanguinity among parents contributes to the elevated incidence of CCHD in MS. Improvement in prenatal screening is another challenge for MS. Because many MS residents live in rural areas with limited access to specialized health care during pregnancy, the need to improve prenatal screening of CCHDs is imperative. Thus development and standardization of novel methods of fetal sonography screening are needed to improve in utero detection of CCHDs and development of novel and cost- effective telehealth-based protocol for echocardiographic (ECHO) prenatal CCHD screening could improve detection rate of CCHDs in underserved areas. The specific aims of this project include: 1) to test the hypothesis that maternal obesity and type II diabetes (DM) contribute to the increased incidence of CCHD in infants in MS; 2) to test the hypothesis that undiagnosed consanguinity among parents in MS contributes to the increased incidence of CCHD in MS; 3) to test the hypothesis that a standardized scoring system utilizing a limited number of sonographic images obtained at routine obstetric evaluation can reliably identify fetuses with CCHD or features suggestive/high risk of CCHD, indicating a need for full echocardiographic evaluation.